Projects per year
Abstract
An anti-solvent screening methodology has been developed to quantitatively evaluate the propensity for precipitation of APIs and their impurities of synthesis during washing. This is illustrated using paracetamol and two typical impurities of synthesis during the washing process. The solubility of paracetamol in different binary wash solutions was measured to provide a basis for wash solvent selection. A map of wash solution composition boundaries for precipitation for the systems investigated was developed to depict where anti-solvent phenomena will take place.
For some crystallisation and wash solvent combinations investigated, as much as 90% of the dissolved paracetamol and over 10% of impurities present in the paracetamol saturated mother liquor was shown to precipitate out. Such levels of uncontrolled crystallisation during washing in a pharmaceutical isolation process can have drastic effect on the final product purity.
Whilst precipitation of both product and impurities from the mother liquor can be avoided by using a solvent in which the API has a solubility similar to that in the mother liquor, for example use of acetonitrile as a wash solvent does not result in any precipitation of the paracetamol API or its impurities. However, the high solubility of paracetamol in acetonitrile, would result in noticeable dissolution of API during washing and would lead to agglomeration during the subsequent drying step. Conversely, use of n-heptane as wash solvent for a paracetamol crystal slurry resulted in the highest amount of precipitation amongst the solvent pairings evaluated. This can be mitigated by designing a multi-stage washing strategy where wash solutions of differing wash solvent concentration are used to minimise step changes in solubility when mother liquor and wash solvent come into contact.
Original language | English |
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Publication status | Published - 9 Oct 2022 |
Event | 13th World Filtration Congress - San Diego, United States Duration: 5 Oct 2022 → 9 Oct 2022 |
Conference
Conference | 13th World Filtration Congress |
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Country/Territory | United States |
City | San Diego |
Period | 5/10/22 → 9/10/22 |
Keywords
- anti-solvent effects
- washing
- active pharmaceutical product purity
- isolation strategy
- anti-solvent effect
- precipitation
- optimisation
Fingerprint
Dive into the research topics of 'Exploring the role of anti-solvent effects during washing on active pharmaceutical product purity'. Together they form a unique fingerprint.Projects
- 3 Finished
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Doctoral Training Partnership (DTP 2016-2017 University of Strathclyde) | Shahid, Muhid
Price, C. J. (Principal Investigator), Lue, L. (Co-investigator) & Shahid, M. (Research Co-investigator)
EPSRC (Engineering and Physical Sciences Research Council)
1/10/17 → 25/08/23
Project: Research Studentship - Internally Allocated
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Future Continuous Manufacturing and Advanced Crystallisation Research Hub (CMAC Hub)
Florence, A. (Principal Investigator), Brown, C. (Co-investigator), Halbert, G. (Co-investigator), Johnston, B. (Co-investigator), Markl, D. (Co-investigator), Nordon, A. (Co-investigator), Price, C. J. (Co-investigator), Sefcik, J. (Co-investigator) & Ter Horst, J. (Co-investigator)
EPSRC (Engineering and Physical Sciences Research Council)
1/01/17 → 30/09/24
Project: Research
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Transforming Industrial Crystallization by Sono-mechanical Manipulation of Crystal Surfaces
Price, C. J. (Fellow)
EPSRC (Engineering and Physical Sciences Research Council)
28/04/14 → 30/08/19
Project: Research Fellowship
Research output
- 1 Poster
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Understanding and mitigating the consequences of undesired crystallisation taking place during washing of active pharmaceuticals
Shahid, M., Sanxaridou, G., Ottoboni, S., Lue, L. & Price, C., 9 Jul 2019, p. 103. 1 p.Research output: Contribution to conference › Poster